2005 ASBMB Fellowship: Stephen Graham

Stephen Graham Stephen completed his Bachelor of Science degree with First Class Honours in 2001 at the University of Sydney. Having majored in both Computer Science and Biochemistry during his undergraduate studies, he decided to forgo the fame and glamour of computer programming to pursue structural biology in his Honours year under the guidance of Dr Mitchell Guss at the Department of Biochemistry (now School of Molecular and Microbial Biosciences). During his Honours year, Stephen investigated the binding of substrate to the proline-specific Escherichia coli metalloenzyme aminopeptidase P (APPro) by refining the crystal structure of APPro in complex with an inhibitor, apstatin. From this structure he was able to determine the mechanism by which apstatin inhibits APPro, and to comment on both the substrate recognition and catalytic mechanism of the enzyme.

Stephen commenced his PhD studies in 2002, remaining in the laboratory of Dr Mitchell Guss. Stephen continued his investigations of APPro, focusing his attention to the problems of substrate recognition by the enzyme and of the relationship between active site metal content and activity, using a variety of techniques to tackle these two problems. Site directed mutagenesis studies and enzyme kinetics studies using non-natural peptides have identified key residues of APPro important for substrate recognition, and have helped define the basis of proline specificity of the enzyme. Enzyme kinetic analysis, quantum chemistry simulations and crystallographic structure determination of APPro loaded with a range of activating and inactivating metals have allowed Stephen to show why manganese activates this enzyme while other metals with similar chemical properties, such as zinc or magnesium, do not.

In addition, Stephen has a keen interest in the role that synchrotron radiation can play in biological research. To learn more about the nuts and bolts of synchrotron radiation, he spent six months in 2003 at the MAX-Lab synchrotron light source in Lund, Sweden, where he actively participated in the development and construction of their new macromolecular crystallography beamline Cassiopeia.

The ASBMB fellowship will allow Stephen to attend the 37th International School of Crystallography meeting entitled 'Evolving Methods in Macromolecular Crystallography' in Erice, Italy.

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This page last modified: October 10, 2008.